Scientists Control Sleep and Social Activity with Light

Optogenetics allows researchers to explore a growing range of behavior.

July 28, 2011

Three new experiments highlight the power of optogenetics—a type of genetic engineering that allows scientists to control brain cells with light.

Karl Deisseroth and colleagues at Stanford University used light to trigger and then alleviate social deficits in mice that resemble those seen in autism. Researchers targeted a highly evolved part of the brain called the prefrontal cortex, which is well connected to other brain regions and involved in planning, execution, personality and social behavior. They engineered cells to become either hyperactive or underactive in response to specific wavelengths of light.

The experimental mice exhibited no difference from the normal mice in tests of their anxiety levels, their tendency to move around or their curiosity about new objects. But, the team observed, the animals in whose medial prefrontal cortex excitability had been optogenetically stimulated lost virtually all interest in engaging with other mice to whom they were exposed. (The normal mice were much more curious about one another.)

The findings support one of the theories behind the neurodevelopmental deficits of autism and schizophrenia; that in these disorders, the brain is wired in a way that makes it hyperactive, or overly susceptible to overstimulation. That may explain why many autistic children are very sensitive to loud noises or other environmental stimuli.

“Boosting their excitatory nerve cells largely abolished their social behavior,” said Deisseroth, [associate professor of psychiatry and behavioral sciences and of bioengineering and the study’s senior author]. In addition, these mice’s brains showed the same gamma-oscillation pattern that is observed among many autistic and schizophrenic patients. “When you raise the firing likelihood of excitatory cells in the medial prefrontal cortex, you see an increased gamma oscillation right away, just as one would predict it would if this change in the excitatory/inhibitory balance were in fact relevant.”

In a second study, from Japan, researchers used optogenetics to make mice fall asleep by engineering a specific type of neuron in the hypothalamus, part of the brain that regulates sleep. Shining light on these neurons inhibited their activity, sending the mice into dreamless (or non-REM) sleep. The research, published this month in the Journal of Neuroscience, might shed light on narcolepsy, a disorder of sudden sleep attacks.

Rather than making mice fall asleep, a third group of researchers used optogenetics disrupt sleep in mice, which in turn affected their memory. Previous research has shown that sleep is important for consolidating, or storing, memories, and that diseases characterized by sleep deficits, such as sleep apnea, often have memory deficits as well. But it has been difficult to analyze the effect of more subtle disruptions to sleep.

The new study shows that “regardless of the total amount of sleep, a minimal unit of uninterrupted sleep is crucial for memory consolidation,” the authors write in the study published online July 25 in the Proceedings of the National Academy of Sciences.

They genetically engineered a group of neurons involved in switching between sleep and wake to be sensitive to light. Stimulating these cells with 10-second bursts of light fragmented the animals’ sleep without affecting total sleep time or quality and composition of sleep.

After manipulating the mice’s sleep, the researchers had the animals undergo a task during which they were placed in a box with two objects: one to which they had previously been exposed, and another that was new to them. Rodents’ natural tendency is to explore novel objects, so if they spent more time with the new object, it would indicate that they remembered the other, now familiar object. In this case, the researchers found that the mice with fragmented sleep didn’t explore the novel object longer than the familiar one — as the control mice did — showing that their memory was affected.

The findings, “point to a specific characteristic of sleep — continuity — as being critical for memory,” said [H. Craig Heller, professor of biology at Stanford and one of the authors of the study.]